RC3H1

ring finger and CCCH-type domains 1, the group of Ring finger proteins|Zinc fingers CCCH-type

Basic information

Region (hg38): 1:173931084-174022357

Links

ENSG00000135870 ∙ NCBI:149041 ∙ OMIM:609424 ∙ HGNC:29434 ∙ Uniprot:Q5TC82 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemophagocytic lymphohistiocytosis, familial, 6 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immune dysregulation and systemic hyperinflammation syndrome	AR	Allergy/Immunology/Infectious	Antibiotics or antiviral agents can be beneficial to treat/prevent infections that can trigger an exaggerated inflammatory response. Chemo/immunotherapy can achieve clinical stability prior to allogeneic hematopoietic cell transplantation (HCT), the only curative therapy.	Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic	31636267

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RC3H1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RC3H1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			59	2	1	62
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	59	3	1

Variants in RC3H1

This is a list of pathogenic ClinVar variants found in the RC3H1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-173938813-T-A		not specified	Uncertain significance (Jan 08, 2025)
1-173938868-A-C		not specified	Uncertain significance (Jul 14, 2021)
1-173941272-T-A		not specified	Uncertain significance (Nov 20, 2024)
1-173941283-T-A		not specified	Uncertain significance (Dec 18, 2024)
1-173941292-G-A		not specified	Uncertain significance (May 30, 2022)
1-173941313-G-C		not specified	Uncertain significance (Jul 08, 2021)
1-173941314-G-A		not specified	Uncertain significance (Oct 09, 2024)
1-173941359-T-A		not specified	Uncertain significance (Dec 17, 2024)
1-173943444-T-C		not specified	Uncertain significance (Jan 10, 2022)
1-173943468-C-T		not specified	Uncertain significance (Aug 02, 2024)
1-173943484-C-G		not specified	Uncertain significance (Jul 14, 2024)
1-173943505-C-A		not specified	Uncertain significance (Feb 09, 2022)
1-173943521-A-G		not specified	Uncertain significance (Dec 28, 2023)
1-173943545-G-A		not specified	Uncertain significance (Jul 13, 2022)
1-173943591-G-C		not specified	Uncertain significance (Jan 24, 2024)
1-173946487-G-A		not specified	Uncertain significance (Feb 22, 2025)
1-173946526-G-C		not specified	Uncertain significance (Jun 02, 2023)
1-173946576-T-C		not specified	Uncertain significance (Nov 09, 2023)
1-173946595-T-C		not specified	Uncertain significance (May 23, 2024)
1-173946821-C-A		not specified	Uncertain significance (Sep 30, 2024)
1-173946833-T-C		not specified	Uncertain significance (Aug 14, 2024)
1-173947386-T-G		not specified	Uncertain significance (Aug 09, 2021)
1-173947390-T-C		not specified	Uncertain significance (Jul 05, 2022)
1-173947392-G-T		not specified	Uncertain significance (Jul 11, 2023)
1-173947411-T-C		not specified	Uncertain significance (Feb 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RC3H1	protein_coding	protein_coding	ENST00000367696	19	91084

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.993	0.00691	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.79	431	628	0.686	0.0000331	7315
Missense in Polyphen		111	233.07	0.47626		2680
Synonymous	1.59	192	222	0.864	0.0000113	2313
Loss of Function	6.28	12	67.7	0.177	0.00000455	663

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000546	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000794	0.0000791
Middle Eastern	0.0000546	0.0000544
South Asian	0.0000653	0.0000653
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF, TNFRSF4 and in many more mRNAs (PubMed:25026078). Cleaves translationally inactive mRNAs harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-independent manner (By similarity). Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs (By similarity). In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity (By similarity). In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression (By similarity). Also recognizes CDE in its own mRNA and in that of paralogous RC3H2, possibly leading to feedback loop regulation (By similarity). Recognizes and binds mRNAs containing an hexaloop stem-loop motif, called alternative decay element (ADE) (By similarity). Able to interact with double-stranded RNA (dsRNA) (PubMed:25504471, PubMed:25026078). miRNA-binding protein that regulates microRNA homeostasis. Enhances DICER-mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression (PubMed:25697406). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2A, UBE2B, UBE2D2, UBE2F, UBE2G1, UBE2G2 and UBE2L3 and produces polyubiquitin chains (PubMed:26489670). Show the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains (PubMed:26489670). {ECO:0000250|UniProtKB:Q4VGL6, ECO:0000269|PubMed:25026078, ECO:0000269|PubMed:25504471, ECO:0000269|PubMed:25697406, ECO:0000269|PubMed:26489670}.

Intolerance Scores

• loftool: 0.305
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.57

Haploinsufficiency Scores

• pHI: 0.377
• hipred: Y
• hipred_score: 0.563
• ghis: 0.493

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.145

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rc3h1
• Phenotype: digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); endocrine/exocrine gland phenotype; neoplasm; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: protein polyubiquitination;nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay;nuclear-transcribed mRNA catabolic process;B cell homeostasis;regulation of germinal center formation;negative regulation of germinal center formation;posttranscriptional regulation of gene expression;negative regulation of B cell proliferation;cytoplasmic mRNA processing body assembly;T cell proliferation;T cell homeostasis;regulation of mRNA stability;negative regulation of T-helper cell differentiation;negative regulation of activated T cell proliferation;lymph node development;spleen development;T cell receptor signaling pathway;regulation of T cell receptor signaling pathway;positive regulation of mRNA catabolic process;3'-UTR-mediated mRNA destabilization;T follicular helper cell differentiation;cellular response to interleukin-1;positive regulation of NIK/NF-kappaB signaling;negative regulation of T-helper 17 cell differentiation;regulation of miRNA metabolic process
• Cellular component: P-body;cytoplasmic stress granule
• Molecular function: RNA binding;double-stranded RNA binding;mRNA 3'-UTR binding;ubiquitin-protein transferase activity;protein binding;zinc ion binding;miRNA binding;RNA stem-loop binding;ubiquitin protein ligase activity